Yuanliang Wang

Depression is a common mood disorder, and growing evidence has revealed the critical role of gut microbiota in its onset and progression. The gut–brain axis, which connects the central nervous system and intestinal microecology, offers new strategies for depression intervention. In this study, an acute depression model was established in mice using lipopolysaccharide (LPS), and the potential antidepressant effects and mechanisms of Bifidobacterium animalis CP-9 were investigated. The results indicated that CP-9 may exert antidepressant effects through multiple pathways, including modulation of peripheral and central inflammatory responses, restoration of gut microbiota balance, enhancement of short-chain fatty acid (SCFA) production, and regulation of neurotransmitter metabolism such as γ-aminobutyric acid (GABA) and 5-hydroxytryptamine (5-HT). Notably, intervention with CP-9 at a dose of 10⁸ CFU/mL significantly alleviated depressive-like behaviors in mice, suggesting its promising potential in the prevention and treatment of mood disorders.

Although mulberry leaf (Morus alba L., ML) and Siraitia grosvenorii (SG) individually demonstrate anti-diabetic properties, their combined efficacy against type 2 diabetes mellitus (T2DM) remains unexplored. This study systematically explored the multi-target mechanisms and synergistic potential of the MLSG combination (MLSG) for T2DM intervention. We evaluated the in vitro inhibitory activities of MLSG, ML, and SG on α-amylase and α-glucosidase, alongside antioxidant capacity assessments through DPPH/ABTS radical scavenging, reducing power, and FRAP assays. Bioactive metabolites were identified using non-targeted metabolomics, while core targets and pathways were predicted using network pharmacology and validated through molecular docking. The results reveal MLSG’s significantly enhanced inhibition of α-amylase (IC₅₀ = 14.06 mg/mL) and α-glucosidase (IC₅₀ = 0.02 mg/mL) compared to individual extracts, exhibiting 1.3–15.5-fold higher potency with synergistic effects (combination index < 1). MLSG also showed improved antioxidant capacity, outperforming SG in DPPH/ABTS⁺ scavenging and reducing power (p < 0.05), and surpassing ML in ABTS⁺ scavenging, reducing power, and FRAP values (p < 0.05). Metabolomics identified 26 MLSG-derived metabolites with anti-T2DM potential, and network analysis pinpointed 26 active components primarily targeting STAT3, AKT1, PIK3CA, EGFR, and MAPK1 to regulate T2DM pathways. Molecular docking confirmed strong binding affinities between these components and core targets. Collectively, MLSG exerts potent synergistic anti-T2DM effects through dual-enzyme inhibition, elevated antioxidant activity, and multi-target pathway regulation, providing a solid foundation for developing MLSG as functional food ingredients.

Theaflavins, benzotropolone compounds formed during black tea processing via catechin condensation, have drawn attention for their potential health benefits and diverse biological effects. This study evaluated the inhibitory effects of four theaflavin monomers—theaflavin-3′-gallate, theaflavin-3,3′-digallate, theaflavin-3-gallate, and theaflavin—on eight CYP450 enzymes using pooled human liver microsomes and specific probe substrates, and seven UGT enzymes using human recombinant UGT enzymes and specific probe substrates. Theaflavin-3′-gallate moderately inhibited CYP1A2-catalyzed phenacetin metabolism and CYP2C8-mediated amodiaquine metabolism, with IC₅₀ values of 8.67 μM and 10–20 μM, respectively. Theaflavin-3,3′-digallate exhibited similar effects. Both compounds showed negligible inhibition with other CYP enzymes. In UGT assays, theaflavin-3′-gallate and theaflavin-3,3′-digallate moderately inhibited UGT1A1- and UGT1A3-mediated beta-estradiol glucuronidation (IC₅₀: 1.40–5.22 μM), with weak or no effects on other UGT enzymes. Molecular docking revealed that CYP1A2-theaflavin-3′-gallate and CYP2C8-theaflavin-3,3′-digallate interactions were non-competitive, primarily mediated by hydrogen bonding and π-interactions. UGT1A1-theaflavin interactions suggested non-competitive inhibition, while UGT1A3-theaflavin interactions indicated competitive inhibition. Other enzyme-theaflavin interactions exhibited minimal binding energy differences, implying mixed-type inhibition. These findings highlight the selective inhibitory effects of theaflavins on specific hepatic enzymes, with potential implications for nutrient interactions, particularly for nutrients metabolized by CYP1A2, CYP2C8, UGT1A1, and UGT1A3. Further research is needed to explore the in vivo relevance and assess the dietary implications of theaflavin-rich black tea in nutrition and metabolism.

Background: Glycolipid metabolism is essential for maintaining metabolic homeostasis. As a new postbiotic, pasteurized Akkermansia muciniphila (P-AKK) is important for the regulation of immunity and metabolism. Objectives: This study aimed to evaluate the effects of P-AKK on glycolipid metabolism in Caenorhabditis elegans fed a high glucose diet. Results: We discovered that feeding nematodes P-AKK improved their healthy lifespan when fed a high-glucose diet. Furthermore, P-AKK contributes to reducing the accumulation of glucose, advanced glycation end products, and lipids and maintains a better physiological state. In addition, P-AKK improved the composition of free fatty acids and decreased the total free fatty acid content of C. elegans. Transcriptome sequencing analysis revealed that P-AKK induced significant enrichment of carbohydrate, oxidative phosphorylation, and fatty acid metabolism pathways. These significantly enriched biological processes were closely related to glucose and lipid metabolism. Among them, P-AKK activated the β-oxidation of fatty acids while inhibiting the de novo synthesis of fatty acids to regulate fatty acid metabolism. Conclusions: The administration of P-AKK positively affected the body phenotypes of C. elegans under high glucose conditions. P-AKK mitigated the fat accumulation induced by a high-glucose diet by regulating key metabolic enzymes, including acyl-CoA synthetase and stearoyl-CoA desaturase.

Glycolipid metabolism is essential for maintaining metabolic homeostasis. As a new generation of probiotics, Akkermansia muciniphila is important for the regulation of immunity and metabolism. This study aimed to evaluate the effects of pasteurized Akkermansia muciniphila (P-AKK) on glycolipid metabolism in Caenorhabditis elegans fed a high glucose diet. We discovered that feeding nematodes P-AKK improved their healthy lifespan when fed a high-glucose diet. Furthermore, P-AKK contributes to reducing the accumulation of glucose and lipids and maintains a better physiological state. In addition, P-AKK improved the composition of free fatty acids and decreased the total fatty acid content of C. elegans. Transcriptome sequencing analysis revealed that P-AKK activated the β-oxidation of fatty acids while inhibiting the de novo synthesis of fatty acids to regulate glycolipid metabolism. The administration of P-AKK positively affected the body phenotypes of C. elegans under high glucose conditions. P-AKK mitigated the fat accumulation induced by a high-glucose diet by regulating key metabolic enzymes, including acyl-CoA synthetase and stearoyl-CoA desaturase.

In Asian regions, areca nuts are tropical fruits that are extensively consumed. The areca nut contains a lot of polyphenols and its safety is unknown. In this research, we investigated the effects of lipopolysaccharides (LPS) and areca nut polyphenols (ANP) on normal RAW264.7 cells. The results showed that LPS stimulated adverse effects in normal cells by affecting cytokine production. The GO analysis results mainly affected DNA repair, cell division, and enzyme activities. In the KEGG analysis results, the NOD-like receptor signaling pathway, which is related to NF-κB, MAPK, and the pro-inflammatory cytokines, is the most significant. In the protein–protein interaction network (PPI) results, significant sub-networks in all three groups were shown to be related to cytokine–cytokine receptor interaction. Collectively, our findings showed a comprehensive understanding of LPS-induced toxicity and the protective effects of ANP by RNA sequencing.

The areca nut is often consumed as a chewing food in the Asian region. Our previous study revealed that the areca nut is rich in polyphenols with high antioxidant activity. In this study, we further assessed the effects and molecular mechanisms of the areca nut and its major ingredients on a Western diet-induced mice dyslipidemia model. Male C57BL/6N mice were divided into five groups and fed with a normal diet (ND), Western diet (WD), WD with areca nut extracts (ANE), areca nut polyphenols (ANP), and arecoline (ARE) for 12 weeks. The results revealed that ANP significantly reduced WD-induced body weight, liver weight, epididymal fat, and liver total lipid. Serum biomarkers showed that ANP ameliorated WD-enhanced total cholesterol and non-high-density lipoprotein (non-HDL). Moreover, analysis of cellular signaling pathways revealed that sterol regulatory element-binding protein 2 (SREBP2) and enzyme 3-hydroxy-3-methylglutaryld coenzyme A reductase (HMGCR) were significantly downregulated by ANP. The results of gut microbiota analysis revealed that ANP increased the abundance of beneficial bacterium Akkermansias and decreased the abundance of the pathogenic bacterium Ruminococcus while ARE shown the opposite result to ANP. In summary, our data indicated that areca nut polyphenol ameliorated WD-induced dyslipidemia by increasing the abundance of beneficial bacteria in the gut microbiota and reducing the expressions of SREBP2 and HMGCR while areca nut ARE inhibited this improvement potential.